FGFR2 is amplified in the NCI-H716 colorectal cancer cell line and is required for growth and survival

Anjili Mathur, Christopher Ware, Lenora Davis, Adi Gazdar, Bo Sheng Pan, Bart Lutterbach

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aberrant kinase activation resulting from mutation, amplification, or translocation can drive growth and survival in a subset of human cancer. FGFR2 is amplified in breast and gastric cancer, and we report here the first characterization of FGFR2 gene amplification in colorectal cancer in the NCI-H716 colorectal cancer cell line. FGFR2 is highly expressed and activated in NCIH716 cells, and FGFR selective small molecule inhibitors or FGFR2 shRNA strongly inhibited cell viability in vitro, indicating "addiction" of NCI-H716 cells to FGFR2. NCI-H716 growth in a xenograft model was also inhibited by an FGFR small molecule inhibitor. FGFR2 was required for activation of multiple downstream signaling proteins including AKT, ERK, S6RP and NFKB. Inhibition of downstream kinases such as AKT or ERK alone had modest effects on proliferation, whereas combined inhibition of AKT and ERK signaling resulted in a loss of viability similar to FGFR2 inhibition. We identified elevated FGFR2 expression in a small subset of primary colorectal cancer, however FGFR2 amplification was not observed. Although FGFR2 amplification is not common in primary colon cancer or lymph node and liver metastases, other subsets of colorectal cancer such as ascites, from which the NCI-H716 cell line was derived, have yet to be tested. These results suggest that emerging FGFR inhibitor therapeutics may have efficacy in a subset of colon cancer driven by FGFR2 amplification.

Original languageEnglish (US)
Article numbere98515
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 26 2014

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colorectal neoplasms
Amplification
Colorectal Neoplasms
Cells
cell lines
Cell Line
Survival
Growth
mitogen-activated protein kinase
Colonic Neoplasms
Phosphotransferases
Chemical activation
Molecules
Gene Amplification
phosphotransferases (kinases)
Ascites
Heterografts
Liver
Small Interfering RNA
Stomach Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

FGFR2 is amplified in the NCI-H716 colorectal cancer cell line and is required for growth and survival. / Mathur, Anjili; Ware, Christopher; Davis, Lenora; Gazdar, Adi; Pan, Bo Sheng; Lutterbach, Bart.

In: PLoS One, Vol. 9, No. 6, e98515, 26.06.2014.

Research output: Contribution to journalArticle

Mathur, Anjili ; Ware, Christopher ; Davis, Lenora ; Gazdar, Adi ; Pan, Bo Sheng ; Lutterbach, Bart. / FGFR2 is amplified in the NCI-H716 colorectal cancer cell line and is required for growth and survival. In: PLoS One. 2014 ; Vol. 9, No. 6.
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